The invention concerns a method for the generation of a convective liquid motion in a fluidic microsystem, especially a method for effecting mixing and turbulence in solutions or particulate suspensions in a fluidic microsystem, which is subjected to the simultaneous formation of electrical and thermal field gradients, and the invention further concerns a fluidic microsystem which is designed to enable the performance of the said method.
Fluidic microsystems find many applications in biochemistry, medicine and biology, especially for analysis of dissolved substances and manipulation of suspended particles. Due to the current miniaturizing and massive parallelization of the functioning processes in microsystems or microchips, special advantages arise for the analysis and synthesis of many biological macromolecules which exist in high combinatorial numbers (refer to G. H. W. Sanders et al., in Trends in Analytical Chemistry, Vol 19/6, 2000, page 364 ff; W. Ehrfeld in Topics in Current Chemistry, publisher, A. Manz et al., Vol. 194, Springer-Verlag, 1998, page 233 ff). Applications in the fluidic microsystems can be found in fundamental research, notably DNA analysis or protein analysis, or even in research of active substances in “combinatorial chemistry”. Additional applications arise in the analysis and the manipulation of individual biological cells or cell groups (see G. Fuhr et al., in Topics in Current Chemistry” publisher, A. Manz et al., Vol. 194, Springer-Verlag, 1998, page 83 ff).
A general problem of fluidic microsystems arises due to the small dimensions of the compartments formed in the microchips, that is, the size of channels, reservoirs and the like, which are measured in the submillimeter range. As a consequence, hydrodynamic liquid flows possess small Reynolds numbers and in turn, liquids move through fluidic Microsystems in laminar flow. If in a microsystem any mixing of liquid does occur, then this is to be ascribed to diffusion of adjacent, laminar flows. In spite of the small dimensions of the microsystem, the diffusion of, for example, biological macromolecules, take place relatively slowly, and on this account, the throughput of the microsystem is severely limited.
An interest exists in achieving convective movement of liquids in a microsystem (such as acquiring turbulence of a liquid or intermixing of a plurality of liquids), which would be carried out with less sluggishness and takes place predominately independent of the characteristics of the liquid and which would assure optical qualities serviceable for observation.
Various approaches are presently known for the introduction of liquid turbulence or the thorough mixing of liquids in Microsystems. The usage of mechanical mixers, as such are employed in the macroworld, is very much limited in Microsystems due to the intense shear and friction. Because of the agglomeration of macromolecules, mechanically movable parts of a microsystem are very prone to failure. Further, as described by W. Ehrfeld, (see above) liquids do intermix by the separation of flows into partial channels, with a subsequent coalescing of the partial channels to bring about a changed spatial arrangement. This technology has the disadvantage, that in the partial channels, once again, the flow is laminar. A fully and thorough mixing is not achieved. S. Shoji describes in Topics in Current Chemistry 1988, (publisher A. Manz et al., Vol. 194, Springer-Verlag, 1998, page 167 ff) an intermixing of liquids by inertial force, for example, a flow in lengthy, very convoluted channels. This technology, however, has the drawback, that the microsystem is handicapped by a complex apparatus. Beyond this, an intermixing of the liquids in the zig-zag channels can be achieved only by means of very high flow velocities (Reynolds number 2-100).
The generation of a convective liquid movement is also known, which is based on the simultaneous buildup of electrical and thermal field gradients in fluidic Microsystems. FIG. 4 shows in a schematic illustration, a conventional system for convective liquid movement, as has been disclosed by WO 00/37165. A compartment 10′ of a fluidic microsystem 100′ has, for example, a throughflow of particulate suspension in the direction of arrow A. In the compartment 10′, it is intended that a turbulence in the liquid will occur. To this end, on the bottom 11′ is provided an electrode arrangement 20′, which is designed for the establishment of electric field gradients transverse to the direction A of flow. At the same time as the generation of these electrical field gradients, the liquid in the compartment 10′ is heated. This heating brings about a thermal gradient and results in a lamination of the of the liquid with differently arranged partial layers corresponding to the thermal gradient. These partial layers, however, also possess different dielectric characteristics. By the action of the electric field gradients, forces are brought to bear on the different partial layers, which effectively lead to a convective turbulence of the liquid. For the development of the thermal gradients, the proposal of WO 00/37165 is to focus a laser beam in the arrow direction B through a transparent cover surface 13′. The liquid heats itself locally, as the desired thermal gradient is formed. The focus point 40′ is located in the liquid with a separating distance allowed from the bottom and the side surfaces, in accord with the double arrow.
Creating convective liquid movement as illustrated in FIG. 4 possesses several faults. This producing of localized heating of the liquid, presupposes a corresponding absorption of the radiation. For many solutions, especially solutions or suspensions of interest in biological applications, a severe limitation of employing a laser for the purposes of radiation exists. A further disadvantage is found in that it may be desired to manipulate or optically detect suspended particles with lasers (optical cases). In some instances, this can lead to mutual interference of the different radiations. Finally, the reproductivity of convection induced by field and radiation means is also limited, since the point of focus for the production of the local heating in the liquid can only be repositioned again with reduced precision.
Thus the purpose of the invention is, to make available an improved method for the generation of a convective motion in a liquid in a fluidic microsystem, wherein the disadvantages of the conventional technologies for achieving thorough mixing or turbulence in liquids are overcome. The method is to especially gain an expanded field of application, in that the convective liquid motion is to be achieved independently of the absorption properties or other characteristics of the liquid in a microsystem, and to be repeatable with a high degree of reproducibility. The purpose of the invention further encompasses an improved microsystem to make this method operable.